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Biomedical subjects

S Abboud

Publications and source records attributed to S Abboud.

At least 19 recordsLinked to original sources
PubMed2006

Parametric EIT for monitoring cardiac stroke volume.

The bio-impedance technique appears appropriate for non-invasive cardiac stroke volume (SV) measurement, as the thoracic conductivity distribution is altered during the cardiac cycle due to the heart contraction and blood perfusion. In the present work, the feasibility of a parametric electrical impedance tomography (EIT) for assessing the cardiac SV was studied. An impedance model of the thorax was constructed from segmented axial MRI images along 19 phases of the cardiac cycle. The heart was simulated as an ellipsoid, with its axes' lengths set as the reconstruction parameters, while all other tissues' geometry and conductivity values were kept fixed. A Newton-Raphson parametric optimization scheme was utilized, yielding a correlation between the reconstructed and anatomical left ventricular volumes of 0.97 (p = 2 x 10(-11)). An analysis of noise sensitivity showed that the proposed algorithm requires an SNR greater than 65 dB. The simulation results were compared to physical data, collected with a portable EIT system (PulmoTrace, CardioInspect). The validation study was employed for a group of N = 28 healthy patients, and a comparison with impedance cardiography measurements (BioZ, Cardiodynamics) was made, showing a correlation of r = 0.86 (p = 4 x10(-9)). The preliminary results demonstrate that parametric EIT has the potential to measure SV, and may be applicable for both clinical and home environment usage.

Algorithms↗
PubMed2006

A portable bio-impedance system for monitoring lung resistivity.

The principles of a hybrid bio-impedance technique are implemented in a novel, lung resistivity monitoring system ("CardioInspect" Tel-Aviv University, Israel). The system is to be utilized in the clinic or at home, for daily monitoring of patients suffering from pulmonary edema. The developed system consists of an eight-electrode belt worn around the thorax, an electronic unit containing analog and digital boards, and a stand-alone DSP based system with a designated software to analyze the data. A Newton-Raphson algorithm based on the finite-volume method is employed for the optimization of the left and right lung resistivity values, making use of the voltage measurements retrieved from opposite current injections. In this preliminary study, 33 healthy volunteers were measured with the system during tidal respiration, yielding symmetric mean left and right lung resistivity values of (1205+/-163, 1200+/-165) (Omega cm). The system reproducibility was better than 2% for both within and between tests measurements, and no dependency between the reconstructed values and various anthropometric parameters was found.

Diagnosis, Computer-Assisted↗
PubMed2005

Heart rate variability (HRV) of patients with traumatic brain injury (TBI) during the post-insult sub-acute period.

OBJECTIVE: To evaluate heart rate variability (HRV) of patients with traumatic brain injury (TBI). METHODS: By a prospective study, the HRV was assessed in 20 patients with TBI during the sub-acute period post-injury (the first test was performed at a mean time post-insult of 38 days) and a matched control. The patients were examined twice, 1 month apart. The assessment included HRV (both in time and frequency domains), GCS, length of coma, brain CT, FIM and FAM. RESULTS: A significant difference was found between patients and controls concerning HRV total power, i.e. frequencies between 0.01-0.6 Hz (high frequency p = 0.003, low frequency p = 0.013, total power p = 0.034) and for standard deviation of RR interval p = 0.011. HRV changes were related more to the timing of the evaluation than to the severity of the brain damage. CONCLUSION: HRV differed of patients with TBI and in the control group. Tendency to HRV normalization changes was detected during the first 3 months after the injury, which suggests recovery of the autonomic nervous system.

Adolescent↗
PubMed2005

CSF-1, RANKL and OPG regulate osteoclastogenesis during murine tooth eruption.

During tooth eruption, osteoclast-mediated bone resorption predominates in alveolar bone along the occlusal surface rather than in bone basal to the tooth. CSF-1, RANKL and OPG, regulatory molecules essential for osteoclastogenesis, are expressed during eruption. However, it is unclear if these cytokines exhibit an expression pattern that correlates with sites of osteoclastogenesis in vivo. To address this issue, mouse mandibles, isolated from 1 to 14 days postnatal, were analysed for osteoclast activity using tartrate-resistant acid phosphatase (TRAP) staining as well as colony-stimulating factor-1 (CSF-1), receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG) mRNA expression using in situ hybridisation. Results showed that CSF-1, RANKL and OPG are expressed in a distinct temporal and spatial manner. In the occlusal region, osteoclast activity was maximal at day 5 and correlated with a relative high expression of CSF-1 and RANKL compared to OPG. In basal bone at this time point, osteoclast activity decreased despite persistent CSF-1 expression and was associated with increased expression of OPG compared to RANKL. By day 8, osteoclastogenesis declined and correlated with upregulation of OPG at the occlusal and basal regions, with this effect continuing throughout eruption. These findings suggest that the spatiotemporal pattern and relative abundance of CSF-1, RANKL and OPG during eruption are key determinants of site-specific osteoclast activity in bone surrounding the tooth. Targeting these cytokines to specific regions in alveolar bone may provide a mechanism for regulating osteoclastogenesis in dental disorders associated with altered tooth eruption.

Acid Phosphatase↗
PubMed2005

Tacrolimus (FK506) versus cyclosporine microemulsion (neoral) as maintenance immunosuppression therapy in kidney transplant recipients.

The effects of the calcineurin inhibitors tacrolimus (FK506) and cyclosporine (Neoral) on graft survival, function, and metabolic profile were evaluated in 69 patients receiving Neoral (group 1) and 54 patients receiving FK506 (group 2) for maintenance immunosuppression following kidney transplantation. Recipient and donor demographics and induction therapy were comparable, except for a higher number of sensitized patients in group 2 (n = 13). Acute rejection timing, severity, and infection rates and types were similar in both groups. During hospitalization, at 6 months, and at 1 year following transplantation, no significant differences were noted between groups in fasting glucose, serum cholesterol levels, triglyceride levels, or need for insulin or antihypertensive therapy. Mean serum creatinine levels on discharge (1.42 mg/dL +/- 0.14 vs 1.68 mg/dL +/- 0.3), at 1 month (1.45 mg/dL +/- 0.1 vs 1.39 mg/dL +/- 0.11), 3 months (1.46 mg/dL +/- 0.09 vs 1.32 mg/dL +/- 0.14), and 1 year (1.29 mg/dL +/- 0.08 vs 1.19 mg/dL +/- 0.09), but not at 6 months (1.42 +/- 0.37 vs 1.10 +/- 0.07; P = .001), were comparable between groups. The 1-year patient and graft survival rates were 98.3% for group 1 and 94.5% for group 2. When evaluated for acute rejection, infection, and metabolic differences, we conclude that both tacrolimus and cyclosporine are effective and safe calcineurin inhibitors for short-term use in kidney transplantation. A similar study is proposed to evaluate the long-term effects of both agents.

Adult↗
PubMed2003

Effect of brain damage and source location on left-right asymmetry of visual evoked potentials in a realistic model of the head.

The left-right asymmetry of visual evoked potentials (VEP) was studied using a realistic three-dimensional model of the head, constructed from CT scans. The integral equation describing the potential distribution due to an inner current-dipole (simulating the VEP source), inside the biological volume conductor (the head) was solved numerically using the finite volume method. The effect of several structural parameters, such as the natural head geometry, the location and orientation of the current source, and conductivity changes (simulating a brain damage) on the VEP asymmetry was examined. The results revealed that the natural anatomical asymmetry presented in a normal head induces some degree of VEP asymmetry (up to 0.42% at the occipital electrodes), yet the major cause of left-right asymmetry is due to asymmetrical location of the source: up to 6.53% in the O(2)-O(1) electrodes for an angular shift of 3 degrees to the left. It was also found that conductivity changes inside the head have a smaller effect on the VEP asymmetry (up to 3.35% in hemorrhaged brain compared to 1.96% in the normal brain at the C(4)-C(3) electrodes). These findings may help in better understanding VEP sources of asymmetry, originating not only due to cerebral functionality, but from structural parameters as well.

Action Potentials↗
PubMed2001

Effect of ischemic stroke on the dynamic beat-to-beat QT-RR relationship.

The ECGs of 26 patients following ischemic stroke and 18 control patients with various orthopedic problems, all without primary heart disease, were examined to characterize the dynamic behavior of uncorrected QT interval in relation to changing RR interval during physiotherapy effort. ECG waveforms were analyzed to extract beat-to-beat QT and RR intervals. Based on performing multiple cross-correlations, the relationship between the RR and QT intervals was calculated using the following general formula QTi = c RRib-1. Linear regression was performed on the logarithms of QT and RR measurements to estimate the constant (a = log c) and the slope (b) values, reflecting the dynamic change of QT during physiotherapy effort. Having these two values, the dynamic QT extrapolated to a heart period of 1 second (QTcd) was calculated. It was found that the mean slope (b) of the linear regression line in the ischemic stroke group was significantly lower than in the control group (0.26 +/- 0.08 vs 0.33 +/- 0.08, P < 0.02), and the constant (a) was significantly higher (1.83 +/- 0.21 for the ischemic stroke vs 1.61 +/- 0.23 for the controls, P < 0.002). No significant difference was found in QTcd values between the two groups (386 +/- 27 ms for the ischemic stroke vs 392 +/- 25 ms for the controls, P > 0.05). In conclusion, hemispheric brain infarction seems to result in alteration in the autonomic activity during exercise manifesting itself as distorted dynamic behavior of the QT interval.

Aged↗
PubMed2000

A novel mammalian iron-regulated protein involved in intracellular iron metabolism.

We have isolated and characterized a novel iron-regulated gene that is homologous to the divalent metal transporter 1 family of metal transporters. This gene, termed metal transporter protein (mtp1), is expressed in tissues involved in body iron homeostasis including the developing and mature reticuloendothelial system, the duodenum, and the pregnant uterus. MTP1 is also expressed in muscle and central nervous system cells in the embryo. At the subcellular level, MTP1 is localized to the basolateral membrane of the duodenal epithelial cell and a cytoplasmic compartment of reticuloendothelial system cells. Overexpression of MTP1 in tissue culture cells results in intracellular iron depletion. In the adult mouse, MTP1 expression in the liver and duodenum are reciprocally regulated. Iron deficiency induces MTP1 expression in the duodenum but down-regulates expression in the liver. These data indicate that MTP1 is an iron-regulated membrane-spanning protein that is involved in intracellular iron metabolism.

Amino Acid Sequence↗
PubMed2000

A computational fluid dynamic model of antigen-antibody surface adsorption on a piezoelectric immunosensor.

A novel computational fluid dynamic model describing the antigen-antibody binding on an electrode surface is presented. It was assumed that the adsorption rate of the antibody sample is dependent upon the flow field in the vicinity of the electrode. Numerical solution of the steady flow in a two-dimensional triangular cell using the Navier-Stokes equations was carried out for predicting mass adsorption on the surface of the crystal. The relationships between the mass adsorbed over the area surface of the electrode, the kinetics of the binding process, and the flow field were determined. The effect of the inlet conditions (location, velocity magnitude, and direction) on the time constant of the mass adsorption process was investigated. It was found that the time constant was decreased by moving the inlet near the edge of the crystal or increasing the normal to the boundary component of the velocity. These changes may significantly reduce the time needed to conduct the test.

Adsorption↗
PubMed1999

Evaluation of impedance technique for detecting breast carcinoma using a 2-D numerical model of the torso.

Previous experimental studies showed that significant changes occur in the electrical properties of breast cancer tissue compared to the surrounding normal tissue. This phenomenon motivated studies on cancer detection using electrical impedance techniques. In the present study, a two-dimensional model of the torso and a numerical method were used to investigate the changes in the potential distribution as a result of a malignant tissue present in the breast. A transverse MRI image of the woman's torso was scanned. Noise reduction and contour-following algorithms were applied to differentiate between eight compartments in the torso. The extracted tissue types were lungs, blood, ribs, bone marrow of the cord, breast fat, skin, skeletal muscle, and heart muscle. Isotropic homogeneous conductivity was assigned to each one of these compartments. The volume conductor problem was solved numerically using the finite volume method to determine the potential distribution developed due to the dipole source. Cases without and with artificially inserted malignant region with realistic sizes were examined to investigate the sensitivity of impedance techniques to detect breast cancer. Significant changes were detected in the potential distribution inside the volume conductor as a result of the realistic size of breast tumors. A linear relation was found between the surface potential in the vicinity of the tumor region and the size of the tumor. For a small malignant area of 0.22 cm2, the surface potential near the tumor region decreased only slightly from a value of 13.81 mV in the normal case to 13.67 mV (0.14 mV change; 1.0%). For a larger malignant area of 5.43 cm2, the potential decrease was more pronounced, 11.29 mV (2.52 mV change; 18.3%), indicating that realistic sizes of breast tumor result in significant changes in the surface potential. Thus, impedance techniques employed in the present study show very good promise in detecting breast cancer.

Algorithms↗
PubMed1999

Real-time PC-based system for dynamic beat-to-beat QT-RR analysis.

A real-time analysis (RTA) system, based on a personal computer with a digital signal processor card (DSP) was developed. The system extracts and saves the QT and RR intervals from an incoming ECG signal sampled at 1 kHz. The method of defining the QT and RR intervals is based on performing multiple cross-correlations that enables rejection of artifacts from the analysis. The relationship between the RR and the QT intervals is found using the following general formula QT(i) cRR(i)(i-1). Linear regression is performed on the logarithms of QT and RR measurements obtained to estimate a constant (a = logc) and a slope (b), reflecting the dynamic change of the QT intervals. Having these two values, the dynamic QT extrapolated to a heart period of 1 s (QTcd) was calculated. The system also performs spectral analysis of the intervals and dynamic QT-RR relation analysis. The system was evaluated on recordings from 10 infants aged 4 to 24 weeks. The QT/RR computerized measuring device used in the present study answers to the requirements for precise dynamic beat-to-beat QT measurement. Its sampling rate is high and can achieve a real millisecond-precision without the need of interpolation methods. The measurements are performed on-line, at the time of the actual recording. Results appear immediately and a measure of dynamic QT behavior can be easily obtained within minutes. The computerized system with the dynamic QT-RR measurements may provide a simple and accurate tool for testing drug treatment and effects of other interventions for cardiac disorders and arrhythmia risk.

Electrocardiography↗
PubMed1999

Evaluation of the impedance technique for cryosurgery in a theoretical model of the head.

Bioimpedance is a noninvasive technique that produces information on the electrical characteristics of tissue inside the body from currents injected and electrical potentials measured on the surface of the body. Because freezing causes a large increase in tissue electrical impedance we thought that it may also cause significant changes in the surface electrical potential making the bioimpedance technique suitable for noninvasive monitoring and imaging of cryosurgery. To evaluate the feasibility of the bioimpedance technique in cryosurgery we examined, as a case study, a theoretical model for the electrical potentials during brain cryosurgery. A three-dimensional spherical model was used to calculate the change in the electrical potential distribution in the head as a function of the current source location and the size of the frozen lesion in the brain. The numerical calculations were executed using the finite volume method and the iterative successive over relaxation method. The results demonstrate that, indeed, freezing inside the head produces measurable changes in the electrical potential on the outer surface-the scalp.

Brain↗
PubMed1999

Functional correlates with left-right asymmetry of visual evoked potentials in stroke patients: modeling and experimental results.

OBJECTIVE: To determine the correlation between a clinical measure of function in patients after first stroke and left-right scalp amplitude of visual evoked potentials using a theoretical model of the head. DESIGN: A random sample of first-stroke patients underwent routine function measurement and investigation of left-right scalp potential asymmetry. Results of the encephalographic tests were compared with those of a healthy subject. To examine the effect of the conductivity in the damaged area on the potential asymmetry, numerical calculations were performed on a model, with four concentric circular compartments representing the brain, cerebrospinal fluid layer, skull, and scalp. The damaged region was modeled as a circular section. SETTING: Neurologic rehabilitation ward of a major rehabilitation hospital and university-affiliated biomedical engineering laboratory. PATIENTS: Four men aged 58 to 71 years, 3 with brain thrombosis and 1 with hemorrhagic stroke. The patients were admitted for rehabilitation an average of 3 weeks after the stroke and stayed for an average of 137 days. Damage was confined to the right brain in all cases; three of the patients had neglect syndrome and/or sensory disturbances. A healthy subject without stroke was also examined. MEASURES: Function was measured with the Functional Independence Measure (FIM) at 48 to 72 hours from admission and during the last week before discharge. Functional gain was calculated by subtracting the FIM admission score from the discharge score. Left-right scalp visual evoked potential amplitude was studied with flash stimuli according to the 10-20 international system and a theoretical model of the head based on two-dimensional computed tomography images; the volume conductor equation was solved numerically using the finite volume method. Left-right potential asymmetry and the damaged-region-to-brain-area ratio were calculated and correlated with the FIM values by linear regression analysis. Negative asymmetry indicates that the activity in the right damaged hemisphere is lower than in the undamaged one. RESULTS: A negative correlation was noted between the FIM score on admission and the left-right scalp potential amplitude asymmetry, and between the FIM gain and the damaged-region-to-brain-area ratio obtained from the computed tomography image. Asymmetry was negative in the thrombotic patients and positive in the hemorrhagic one. The healthy subject showed nonsignificant asymmetry. CONCLUSION: A relationship might exist between the left-right asymmetry of the scalp visual evoked potential and both the damaged-region-to-brain-area ratio and the functional outcome of rehabilitation in poststroke patients. The modeling study shows that the left-right asymmetry is most likely the result of changes in the conductivity at the damaged area, which, in turn, are probably associated with patient functional status and evolution. Further validation in larger groups of patients and normal subjects is needed before these parameters can serve as useful indices for clinical purposes.

Aged↗
PubMed1999

A comparison of a new transtelephonic portable spirometer with a laboratory spirometer.

The Spirophone is a new, portable transtelephonic spirometer which records the slow and the forced expiratory vital capacity tests. Data can be transmitted via the telephone to a remote receiving centre, where a volume-time curve and the flow-volume curve are displayed on screen in real time. The aim of this study was to compare the newly developed transtelephonic spirometer, with a laboratory spirometer according to the American Thoracic Society (ATS) testing guidelines. Spirometry indices (slow vital capacity (SVC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), forced expiratory flow at 25, 50 and 75% of FVC (FEF25, FEF50, and FEF75, respectively)) were measured from the SVC and the FVC tests in 45 subjects (30 patients, 15 healthy volunteers) according to the ATS standards. The data obtained with the laboratory system were compared to those from the Spirophone. The Spirophone measurements of SVC, FVC, FEV1, PEF, FEF25, FEF50 and FEF75 correlated closely (r=0.91-0.98) to those from the laboratory system, whereas FEF25, FEF50, and FEF75 were significantly higher with the Spirophone. It is concluded that the Spirophone is comparable to the standard spirometry for home monitoring of slow vital capacity, forced vital capacity, forced expiratory volume in one second and peak expiratory flow. The validity of the manoeuvre can be assessed on screen in real time.

Adult↗
PubMed1999

Potential role of insulin-like growth factor binding protein-4 in the uncoupling of bone turnover in multiple myeloma.

Decreased bone formation plays an important role in the development of lytic lesions during the late stage of multiple myeloma (MM). Release of insulin-like growth factor binding protein-4 (IGFBP4) by tumour cells adjacent to bone may inhibit IGF-I-stimulated osteoblast growth and contribute to decreased bone formation. The present study demonstrates that the human MM cell line, ARH-77, expresses IGFBP4 and, to a lesser extent, IGFBP6 mRNA and protein. IGFBP4 expression in myeloma cells may be modulated by cytokines released by stromal cells and T cells in the microenvironment. We tested the effect of recombinant interferon-gamma (INF) on IGFBP4 expression in ARH-77. INF increased IGFBP4 mRNA and protein levels at 12 h, with a decline to baseline by 24 h. In contrast, IGFBP4 was not regulated in response to IL-6, TNF-alpha, PDGF BB, bFGF, TGF-beta or the cAMP agonist, forskolin. In other systems. IGFBP4 may also be regulated post-transcriptionally by a protease that is activated by IGF-I or -II. Conditioned medium from ARH-77 cultures incubated with IGF-I or -II for up to 24 h failed to demonstrate proteolytic activity. Proteolysis was also not observed when conditioned medium containing exogenous rhIGFBP4 was incubated with IGF-I or -II under cell-free conditions. To determine if human myeloma tumours also express IGFBP4, total RNA was isolated from four tumour biopsies. All samples expressed detectable levels of IGFBP4 mRNA. These findings indicate that interferon-gamma may indirectly modulate bone formation via the the release of tumour-derived IGFBP4. suggesting that the immune system may influence bone turnover in MM. Failure of myeloma cells to release protease activity may promote IGFBP4 accumulation in the microenvironment during tumour growth.

Bone Remodeling↗
PubMed1999

Dynamic beat-to-beat QT-RR relationship during physiotherapy effort in elderly patients without primary heart disease.

The ECGs from 18 patients hospitalized in a rehabilitation setting, following surgery for hip fracture, were examined to characterize the dynamic behavior of uncorrected QT interval in relation to changing RR interval during physiotherapy effort. ECG waveforms were analyzed to extract beat-to-beat QT and RR intervals using a computerized ECG Analyzer (CEA-1100). The method of defining the QT and RR intervals is based on performing multiple cross-correlations that enable rejection of artifacts from the analysis. The relationship between the RR and QT intervals was found using the following general formula QTi = cRRi-1b. Linear regression was performed on the logarithms of QT and RR measurements obtained to estimate the constant (a = log c) and the slope (b) values, reflecting the dynamic change of QT during physiotherapy effort. Having these two values, the dynamic QT extrapolated to a heart period of 1 second (QTcd) was calculated. The results were compared to the conventional corrected static QT according to the Bazzet formula (QTcs). The mean values of constants (a = log c) and slopes (b) over all patients were found to be 1.61 +/- 0.23 and 0.33 +/- 0.08, respectively, giving a QT (ms) heart-period (ms) dynamic relation of QTi = 41 x RR(i-1)0.33. The correlation between the dynamic QT and the static QT intervals was not significant. The mean values of the QTcd and QTcs intervals were significantly different (392 +/- 25 ms vs 434 +/- 28 ms; P < 0.0001). This dynamic measurement method of QT intervals may provide additional information on normal and abnormal cardiac repolarization in health and disease, helping in the diagnosis of cardiac disorders and arrhythmia risk.

Aged↗
PubMed1998

Characterization and regulation of insulin-like growth factor binding proteins in human hepatic stellate cells.

Cultured hepatic stellate cells (HSCs), the cell type primarily involved in the progression of liver fibrosis, secrete insulin-like growth factor-I (IGF-I) and IGF binding protein (IGFBP) activity. IGF-I exerts a mitogenic effect on HSCs, thus potentially contributing to the fibrogenic process in an autocrine fashion. However, IGF-I action is modulated by the presence of specific IGFBPs that may inhibit and/or enhance its biologic effects. Therefore, we examined IGFBP-1 through IGFBP-6 mRNA and protein expression in HSCs isolated from human liver and activated in culture. Regulation of IGFBPs in response to IGF-I and other polypeptide growth factors involved in the hepatic fibrogenic process was also assessed. RNase protection assays and ligand blot analysis demonstrated that HSCs express IGFBP-2 through IGFBP-6 mRNAs and release detectable levels of IGFBP-2 through IGFBP-5. Because IGF-I, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-beta (TGF-beta) stimulate HSC proliferation and/or matrix production, we tested their effect on IGFBPs released by HSCs. IGF-I induced IGFBP-3 and IGFBP-5 proteins in a time-dependent manner without an increase in the corresponding mRNAs. IGFBP-4 protein levels decreased in response to IGF-I. TGF-beta stimulated IGFBP-3 mRNA and protein but decreased IGFBP-5 mRNA and protein. In contrast, PDGF-BB failed to regulate IGFBPs compared with controls. Recombinant human IGFBP-3 (rhIGFBP-3) was then tested for its effect on IGF-I-induced mitogenesis in HSCs. rhIGFBP-3 inhibited IGF-I-stimulated DNA synthesis in a dose-dependent manner, with a peak effect observed at 25 nM IGFBP-3. Because TGF-beta is highly expressed in cirrhotic liver tissue, we determined whether IGFBP-3 mRNA expression is increased in liver biopsies obtained from patients with an active fibroproliferative response due to viral-induced chronic active hepatitis. In the majority of these samples, IGFBP-3 mRNA was increased compared with normal controls. These findings indicate that human HSCs, in their activated phenotype, constitutively produce IGFBPs. IGF-I and TGF-beta differentially regulate IGFBP-3, IGFBP-4, and IGFBP-5 expression, which, in turn, may modulate the in vitro and in vivo action of IGF-I.

Adipocytes↗